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Mutational change of CTX-M-15 to CTX-M-127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient

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@article{b12d1886ab134df2af4ddf5523e5d94a,
title = "Mutational change of CTX-M-15 to CTX-M-127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient",
abstract = "Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.",
keywords = "Escherichia coli, LPS, mecillinam, metabolism, mutation, O-antigen, Pivmecillinam, resistance, serotype, whole-genome sequencing",
author = "Nielsen, {Karen Leth} and Hansen, {Katrine Hartung} and Nielsen, {Jesper Boye} and Knudsen, {Jenny Dahl} and Kristian Sch{\o}nning and Niels Frimodt-M{\o}ller and Hertz, {Frederik Bo{\"e}tius} and Filip Jans{\aa}ker",
note = "{\circledC} 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.",
year = "2019",
month = "12",
doi = "10.1002/mbo3.941",
language = "English",
volume = "8",
pages = "1--4",
journal = "MicrobiologyOpen",
issn = "2045-8827",
publisher = "John Wiley and Sons Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - Mutational change of CTX-M-15 to CTX-M-127 resulting in mecillinam resistant Escherichia coli during pivmecillinam treatment of a patient

AU - Nielsen, Karen Leth

AU - Hansen, Katrine Hartung

AU - Nielsen, Jesper Boye

AU - Knudsen, Jenny Dahl

AU - Schønning, Kristian

AU - Frimodt-Møller, Niels

AU - Hertz, Frederik Boëtius

AU - Jansåker, Filip

N1 - © 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

PY - 2019/12

Y1 - 2019/12

N2 - Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.

AB - Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in blaCTX-M-15 to blaCTX-M-127 , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.

KW - Escherichia coli

KW - LPS

KW - mecillinam

KW - metabolism

KW - mutation

KW - O-antigen

KW - Pivmecillinam

KW - resistance

KW - serotype

KW - whole-genome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85073931705&partnerID=8YFLogxK

U2 - 10.1002/mbo3.941

DO - 10.1002/mbo3.941

M3 - Journal article

VL - 8

SP - 1

EP - 4

JO - MicrobiologyOpen

JF - MicrobiologyOpen

SN - 2045-8827

IS - 12

M1 - e941

ER -

ID: 58060601